A Phase I/II Trial of Neoadjuvant Paclitaxel, Carboplatin and OSI-774 (Tarceva) With Concurrent Accelerated Hyperfractionation Radiation Followed by Maintenance Therapy With OSI-774 for Stage III Non-Small Cell Lung Cancer
18 Years
N/A
Both
Lung Cancer
Trial Information
A Phase I/II Trial of Neoadjuvant Paclitaxel, Carboplatin and OSI-774 (Tarceva) With Concurrent Accelerated Hyperfractionation Radiation Followed by Maintenance Therapy With OSI-774 for Stage III Non-Small Cell Lung Cancer
OBJECTIVES:
Primary
- Assess the safety and feasibility of erlotinib hydrochloride, paclitaxel, and
carboplatin in combination with accelerated hyperfractionated radiotherapy in patients
with stage IIIA or IIIB non-small cell lung cancer.
- Determine the maximum tolerated dose and recommended phase II dose of erlotinib
hydrochloride in these patients.
- Assess the safety and tolerability of long-term maintenance erlotinib hydrochloride
after completion of adjuvant chemoradiotherapy in these patients.
Secondary
- Evaluate the clinical and pathological response rate in these patients after
neoadjuvant erlotinib hydrochloride, paclitaxel, carboplatin, and radiotherapy.
- Assess the impact of erlotinib hydrochloride on disease-free survival, overall
survival, locoregional control, and distant metastatic control in these patients.
OUTLINE: This is an open-label, phase I dose-escalation study of erlotinib hydrochloride
followed by a non-randomized phase II study.
Cohorts of 3-6 patients receive escalating doses of erlotinib hydrochloride until the
maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at
which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.
- Phase I:
- Neoadjuvant chemoradiotherapy: Patients receive oral erlotinib hydrochloride once
daily on days 1-28 and paclitaxel IV over 1 hour and carboplatin IV over 30
minutes on days 1, 8, and 15 in the absence of disease progression or unacceptable
toxicity. Patients concurrently undergo radiotherapy twice daily on days 1-5 and
8-12. Patients with complete response, partial response, or stable disease proceed
to surgery. Patients who develop a medical contraindication to surgery (i.e.,
medically unresectable) receive a second course of erlotinib hydrochloride,
paclitaxel, carboplatin, and radiotherapy as above within 2 weeks after completion
of neoadjuvant chemoradiotherapy.
Cohorts of 3-6 patients receive escalating doses of erlotinib hydrochloride until the
maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at
which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.
- Surgery: Within 4 weeks after completion of neoadjuvant chemoradiotherapy, patients
undergo surgical resection and then proceed to adjuvant chemoradiotherapy.
- Adjuvant chemoradiotherapy: Within 6-8 weeks after surgery, patients receive a second
course of erlotinib hydrochloride, paclitaxel, carboplatin, and radiotherapy as in
neoadjuvant chemoradiotherapy.
- Maintenance therapy: All patients receive oral erlotinib hydrochloride once daily for 2
years in the absence of disease progression or unacceptable toxicity.
- Phase II: Patients receive treatment as in phase I with erlotinib hydrochloride at
the MTD.
After completion of study treatment, patients are followed periodically.
PROJECTED ACCRUAL: A total of 42 patients will be accrued for this study.
Inclusion Criteria
DISEASE CHARACTERISTICS:
- Histologically or cytologically confirmed non-small cell lung cancer
- Surgically determined stage IIIA or IIIB disease
- Histology from an involved mediastinal or supraclavicular lymph nodes alone will
be allowed if a separate distal primary lesion is clearly evident on radiographs
- Histological or cytological proof of mediastinal nodal involvement by
mediastinoscopy, Chamberlain procedure, thoracoscopy, thoracotomy, or
CT-guided biopsy is required except for cases of paralysis of left true
vocal cord with separate left lung primary distinct from enlarged nodes > 1
cm in the anterior-posterior window seen on the CT scan
- Patients with N3 or T4 status must be evaluated and deemed potentially resectable
after induction chemotherapy and radiation therapy
- Measurable and evaluable disease
- No malignant pleural effusion except for effusion visible only on CT scan and deemed
too small to tap
- No pericardial effusion
- No small or mixed small cell/non-small cell lung cancer
- No massive lesions requiring radiation to the entire lung
- No metastatic cancer to the lungs
PATIENT CHARACTERISTICS:
- ECOG performance status 0-1
- WBC ≥ 3,000/mm^3
- Platelet count > 100,000/mm^3
- Serum creatinine ≤ 2.0 mg/dL
- Alkaline phosphatase, AST, and ALT < 2 times upper limit of normal
- Albumin > 3.0 g/dL
- Serum bilirubin < 1.5 mg/dL
- Adequate pulmonary function
- No clinical evidence of another uncontrolled malignancy
- No requirement for urgent therapy for severe local symptoms such as post-obstructive
pneumonia
PRIOR CONCURRENT THERAPY:
- No prior chemotherapy, radiation therapy, or immunotherapy for lung cancer
- No prior surgery to treat the cancer
Type of Study:
Interventional
Study Design:
Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
Maximum tolerated dose of erlotinib hydrochloride (Phase I)
Outcome Description:
The Phase I portion of this study is to determine the Maximum Tolerated Dose (MTD) of combining OSI-774 with the paclitaxel-carboplatin chemoradiation protocol and to assess the safety and feasiblity of this combination.
Outcome Time Frame:
2 weeks after surgery
Safety Issue:
Yes
Principal Investigator
Nathan Pennell, MD
Investigator Role:
Study Chair
Investigator Affiliation:
Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center
Authority:
United States: Food and Drug Administration
Study ID:
CCF5876
NCT ID:
NCT00278148
Start Date:
October 2005
Completion Date:
December 2012
Related Keywords:
- Lung Cancer
- stage IIIA non-small cell lung cancer
- stage IIIB non-small cell lung cancer
- Carcinoma, Non-Small-Cell Lung
- Lung Neoplasms
Name | Location |
|---|---|
| Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center | Cleveland, Ohio 44195 |
